Nusinersen stabilises respiratory function in paediatric spinal muscular atrophy

Abstract

Respiratory effects of nusinersen in Spinal Muscular Atrophy (SMA) are largely unknown. Aim: To assess change in respiratory function in pediatric SMA in year 1 of nusinersen treatment & compare to pre-treatment decline rate. Methods: 12-month prospective study of all childhood SMA type 1-3 in Queensland, Australia from 2018. Peripheral muscle strength tests performed prior to & 4 occassions during study with age appropriate respiratory tests attained each visit. Full diagnostic Polysomnography conducted initially & study completion. Lung function 2 years prior to study collected retrospectively. Rates of lung function decline compared prior to & following comencement of nusinersen. Comparisons made between PSG pre & post 12 months treatment. Muscle strength responders & non-responders compared for respiratory parameter change. 31 children included (18 males, 0.25-18.8 years old), 19% SMA type 1, 52% type 2 & 29% type 3. Annual rate decline of Forced Vital Capacity (FVC) z-score reduced for SMA type 2 (p=0.009) and type 3 SMA (p=0.3). Mean total apnoea-hypopnoea index reduced in type 1 [12.3 events/hour to 3.7], type 2 [4.5 (SD 3.0 95% CI 1.8-7.3) to 2.9 (SD 3.0 CI 0.1-5.6) p=0.1] and type 3 [5.3 (SD 2.2 95% CI0.14-10.8) to 2.5 (SD 19.98 95%CI 4.34) p=0.4]. No change in FVC z-score between responders and non-responders was noted (FVC z-score 0.5 p=0.5 95%CI -1.2-2.1 r<0.001 and 0.1 p=0.9 95%CI -2.4-2.6 r=0.01 respectively). Conclusion: Nusinersen stabilises lung function, halts progressive decline seen before treatment in type 2 and 3 SMA. Lung function stability seen even in those without peripheral muscle strength response. Improvements in sleep disordered breathing seen in type 1-3.L6338016882021-01-05 <br />